-
International Journal of Molecular... Jan 2023α-thalassemia is characterized in about 80% of cases by deletions generated by the presence of duplications and interspersed repeated sequences in the α-globin gene...
α-thalassemia is characterized in about 80% of cases by deletions generated by the presence of duplications and interspersed repeated sequences in the α-globin gene cluster. In a project on the molecular basis of α-thalassemia in Southern Italy, we identified six families, showing an absence of the most common deletions, and normal α-globin gene sequences. Multiplex Ligation-dependent Probe Amplification (MLPA), qRT-PCR, and the sequencing of long-range PCR amplicon have been used for the identification and characterization of new deletions. MLPA analysis for the identification of α- and β-globin rearrangement revealed the presence of five new α-thalassemia deletions. The set-up of qRT-PCR allowed us to delimit the extent of the deletions ranging from about 10 kb to more than 250 kb, two of them being of the telomeric type. The long-range PCR generated a specific anomalous fragment in three deletions, and only several unspecific bands in the other two deletions. The sequencing of the anomalous amplicons revealed the breakpoints of two deletions: the --PA, 34 kb long, identified in two families, and the telomeric --AG, 274 kb long. The anomalous fragment containing the breakpoint of the deletion --FG was partially sequenced, and it was not possible to identify the breakpoints due to the presence of several repetitive Alu sequences. The analysis of the breakpoint regions of the --Sciacca and --Puglia, respectively, are about 10 and 165 kb long, and revealed the presence of repeats that most likely impaired the amplification of a specific fragment for the identification of the breakpoint. MLPA, in association with qRT-PCR and long-range PCR, is a good approach for the identification and molecular characterization of rare or new deletions. Breakpoint analysis confirms that Alu sequences play an important role in favoring unequal crossing-over. Southern Italy shows considerable genetic heterogeneity, as expected with its central position in the Mediterranean basin, favoring migratory flows.
Topics: Humans; alpha-Thalassemia; alpha-Globins; Multigene Family; Multiplex Polymerase Chain Reaction; Italy
PubMed: 36768900
DOI: 10.3390/ijms24032577 -
Hemoglobin Mar 2020Hb S (: c.20A>T) and α- and/or β-thalassemia (α- and/or β-thal) coinheritance is a common genetic disorder in regions with a high prevalence of thalassemia and...
Hb S (: c.20A>T) and α- and/or β-thalassemia (α- and/or β-thal) coinheritance is a common genetic disorder in regions with a high prevalence of thalassemia and sickle cell disease. The clinical manifestations of this coinheritance vary from mild to severe complications. Iran is a country with a high incidence of thalassemia and sickle cell disease. This study aimed to evaluate the coinheritance of sickle cell disease with α- and/or β-thal in Iranian patients. In this cross-sectional study from 2018-2019, a total of 47 participants with the Hb S abnormality, who were referred to the Zafar Thalassemia Clinic (Tehran, Iran), were selected as a study group. Molecular analysis for the evaluation of α and β gene mutations was performed in all participants. Hb SS, Hb S/β-thal and Hb S/Hb D-Punjab (also known as Hb D-Los Angeles, Hb D-Chicago, Hb D-North Carolina, Hb D-Portugal and Hb Oak Ridge) (: c.364G>C) were detected in 21 (44.7%), 23 (48.9%) and three (6.4%) patients, respectively. α Gene mutations were also detected in five patients with Hb S/β-thal, four patients with sickle cell disease and one patient with Hb S/Hb D-Punjab. In the current study, -α/αα with β gene abnormalities was the most common genotype. Our study showed that the coinheritance of sickle cell disease with α- and β-thal is common and evaluation of these disorders, especially in pre marriage screening is important for diagnosis and management strategies.
Topics: Anemia, Sickle Cell; Cross-Sectional Studies; Genetic Predisposition to Disease; Hemoglobin, Sickle; Hemoglobins, Abnormal; Humans; Iran; Mutation; Polymorphism, Single Nucleotide; alpha-Thalassemia; beta-Globins; beta-Thalassemia
PubMed: 32370567
DOI: 10.1080/03630269.2020.1757462 -
Archives of Razi Institute Jun 2022The prevalence of alpha-thalassemia as a major health problem in the south of Iraq has highlighted the necessity of investigations and screening of patients with...
The prevalence of alpha-thalassemia as a major health problem in the south of Iraq has highlighted the necessity of investigations and screening of patients with thalassemia. The present study aimed to characterize the spectrum of alpha-globin gene mutations in patients who were followed up in a genetic diseases center in Thi-Qar province. A total of 30 subjects were collected from thalassemia patients and 15 cases as the control group. Polymerase chain reaction (PCR) and direct sequencing were performed for functionally regions of the gene (exon 1 and exon 2). The fragment size amplified was 442 bp in the Exon 1 region and 324 bp in the Exon 2 region of α-globin. The molecular analysis of the sequence of PCR products revealed that 13 point mutation within the α-thalassemia gene included deletion and substitution mutation, while the rest of the mutations were in the intron site of the gene. These results indicated that mutations may constitute a risk of developing hemophilia B disease. Molecular mechanisms in the expression of globin genes are used to help manage patients with thalassemia.
Topics: alpha-Globins; alpha-Thalassemia; Iraq; Mutation; Point Mutation; Humans
PubMed: 36618297
DOI: 10.22092/ARI.2022.357209.1997 -
Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... Mar 2020Alpha-thalassemia is an autosomal recessive genetic disease as well as a relatively common hemoglobinopathy. Severe alpha-thalassemia (also known as Hb Bart's Hydrops...
Alpha-thalassemia is an autosomal recessive genetic disease as well as a relatively common hemoglobinopathy. Severe alpha-thalassemia (also known as Hb Bart's Hydrops fetalis syndrome) and intermediate alpha-thalassemia (also known as Hb H disease) are among the most common birth defects in southern China. To implement carrier screening and large population prevention program in high incidence areas can significantly reduce the incidence of alpha-thalassemia. This guideline was established by combining the discoveries of basic research, clinical research and guidelines from other countries and the actual data of Chinese population. It has summarized the medical genetics knowledge and key points in the clinical treatment for alpha-thalassemia, and provided suggestions for the clinical diagnosis and standard management of patients.
Topics: China; Genetics, Medical; Hemoglobins, Abnormal; Humans; Hydrops Fetalis; Practice Guidelines as Topic; alpha-Thalassemia
PubMed: 32128738
DOI: 10.3760/cma.j.issn.1003-9406.2020.03.003 -
International Journal of Hematology Sep 2021This study investigated prenatal diagnosis of α-thalassemia and β-thalassemia in 3049 families in 18 regions of Hainan Province. Molecular diagnosis was performed in...
This study investigated prenatal diagnosis of α-thalassemia and β-thalassemia in 3049 families in 18 regions of Hainan Province. Molecular diagnosis was performed in 3049 couples with thalassemia in Hainan Province. Genomic DNA was extracted from peripheral blood of the couples and villus, amniotic fluid, or cord blood of fetuses. DNA-based diagnosis was performed using polymerase chain reaction. The most commonly detected mutation for α-thalassemia was- SEA/αα (31.53%), followed by - α4.2/αα (11.15%) and - α3.7/αα (11.02%). The most common mutation for β-thalassemia was CD41/42 (30.27%), followed by - 28 (2.56%). Prevalence was highest in the coastal regions and lowest in the Wenchang, Lingao, and Ding'an regions. We also found that the most common gene mutations in Han people and other minority groups were not homogeneous. Prenatal diagnosis showed 556 normal fetuses, 116 with α-thalassemia hydrops, and 134 with β-thalassemia major. Our findings provide important information for clinical genetic counseling regarding prenatal diagnosis for thalassemia major in Hainan Province.
Topics: China; Female; Genotype; Geography, Medical; Heterozygote; Humans; Male; Mutation; Pregnancy; Prevalence; alpha-Globins; alpha-Thalassemia; beta-Globins; beta-Thalassemia
PubMed: 34195938
DOI: 10.1007/s12185-021-03173-z -
International Journal of Laboratory... Aug 2023Thalassemia is the most common monogenic disease in South and Southeast Asia. An accurate assessment of the relative frequency and composition of thalassemia mutations...
INTRODUCTION
Thalassemia is the most common monogenic disease in South and Southeast Asia. An accurate assessment of the relative frequency and composition of thalassemia mutations is important for the design of appropriate strategies to prevent the disease. In this study, we aimed to decode the molecular characterization of thalassemia mutations in Zhuhai region of southern China.
METHODS
A total of 8048 individuals who were potential thalassemia carriers were enrolled. Gap-polymerase chain reaction (Gap-PCR) and reverse dot-blot (RDB) hybridization methods were employed to detect common deletional and non-deletional thalassemia mutations. Multiplex ligation dependent probe amplification (MLPA) and Sanger sequencing were used to analyze and verify rare and complex mutations.
RESULTS
We diagnosed 3433 individuals as thalassemia carriers or patients. Of these, 2395 (69.76%) individuals with α-thalassemia harbored 13 α-globin gene mutations. The three most common α-thalassemia mutations were -- (60.08%), -α (20.62%) and -α (9.25%). We diagnosed 903 (26.30%) individuals with β-thalassemia and identified 20 β-globin gene mutations, of which the three most frequent were CD41/42 (-TCTT) (38.10%), IVS-II-654 (C>T) (23.69%) and TATAbox-28 (A>G) (15.18%). In addition, we identified 15 rare thalassemia variants. We also summarized the association between the thalassemia genotype and hematological parameters, which demonstrated the broad phenotypic heterogeneity caused by globin gene mutations.
CONCLUSION
This is the first survey of thalassemia molecular epidemiology and hematological phenotype in Zhuhai region. It uncovered a high prevalence and complex molecular spectrum of thalassemia. These findings can be used as a basis for thalassemia diagnosis, counseling and prevention management.
Topics: Humans; beta-Thalassemia; alpha-Thalassemia; Genotype; Heterozygote; Mutation; China
PubMed: 36918023
DOI: 10.1111/ijlh.14059 -
Neuropediatrics Apr 2022This study explores the prevalence, clinical characteristics, and treatment of epilepsy and sleep disorders in α thalassemia mental retardation (ATR-X) syndrome.
BACKGROUND
This study explores the prevalence, clinical characteristics, and treatment of epilepsy and sleep disorders in α thalassemia mental retardation (ATR-X) syndrome.
DESIGN
In this cross-sectional study, 37 participants with ATR-X syndrome aged 1.8 to 44 years were studied using a customized epilepsy questionnaire, review of electroencephalography (EEG) findings, the modified Sleep Questionnaire of Simonds and Parraga and 2-week sleep diary.
RESULTS
Eleven participants had a clinical diagnosis of generalized epilepsy (29.7%). Seizure types were generalized tonic-clonic seizures, absences, and myoclonia. Interictal EEG recordings in participants with GTCS showed no epileptic discharges in 78%. Similarly, EEG recordings during myoclonia and absences often demonstrated no epileptic discharges. Sleep problems (difficulty falling or maintaining sleep, and early awakening) were reported in 70%. Participants with reported sleep problems went to bed earlier ( = 0.027) and had a lower sleep efficiency ( < 0.01) than participants without sleep problems, but as a group they both had a sufficient total sleep time (9 hours and 52 minutes vs. 10 hours and 55 minutes). Sixteen participants (43.2) used medication to improve sleep (predominantly melatonin = 10), being effective in only two.
CONCLUSION
One-third of participants with ATR-X syndrome had a clinical diagnosis of epilepsy, but the absence of EEG abnormalities in suspected epileptic seizures questions this diagnosis in these patients. EEG recording during seizure like symptoms is warranted before making an epilepsy diagnosis. Seventy percent experienced sleep problems, although total sleep time was normal in most participants. Long bedtimes might have a negative influence on sleep efficiency.
Topics: Ataxia Telangiectasia Mutated Proteins; Cross-Sectional Studies; Electroencephalography; Epilepsy; Epilepsy, Generalized; Humans; Mental Retardation, X-Linked; Myoclonus; Seizures; Sleep; Sleep Wake Disorders; alpha-Thalassemia
PubMed: 34933379
DOI: 10.1055/s-0041-1740551 -
International Journal of Environmental... Oct 2020Alpha(α)-thalassemia is a blood disorder caused by many types of inheritable α-globin gene mutations which causes no-to-severe clinical symptoms, such as Hb Bart's... (Meta-Analysis)
Meta-Analysis
Alpha(α)-thalassemia is a blood disorder caused by many types of inheritable α-globin gene mutations which causes no-to-severe clinical symptoms, such as Hb Bart's hydrops fetalis that leads to early foetal death. Therefore, the aim of this meta-analysis was to provide an update from year 2010 to 2020 on the prevalence of α-thalassemia in Southeast Asia. A systematic literature search was performed using PubMed and SCOPUS databases for related studies published from 2010 to 2020, based on specified inclusion and exclusion criteria. Heterogeneity of included studies was examined with the I2 index and Q-test. Funnel plots and Egger's tests were performed in order to determine publication bias in this meta-analysis. Twenty-nine studies with 83,674 subjects were included and pooled prevalence rates in this meta-analysis were calculated using random effect models based on high observed heterogeneity (I2 > 99.5, -value < 0.1). Overall, the prevalence of α-thalassemia is 22.6%. The highest α-thalassemia prevalence was observed in Vietnam (51.5%) followed by Cambodia (39.5%), Laos (26.8%), Thailand (20.1%), and Malaysia (17.3%). No publication bias was detected. Conclusions: This meta-analysis suggested that a high prevalence of α-thalassemia occurred in selected Southeast Asia countries. This meta-analysis data are useful for designing thalassemia screening programs and improve the disease management.
Topics: Asia, Southeastern; Humans; Prevalence; alpha-Thalassemia
PubMed: 33050119
DOI: 10.3390/ijerph17207354 -
Hemoglobin Jul 2021We present case histories of three patients who had β-thalassemia (β-thal) trait with 'unusual severity' managed as β-thal intermedia (β-TI) where the basis of...
We present case histories of three patients who had β-thalassemia (β-thal) trait with 'unusual severity' managed as β-thal intermedia (β-TI) where the basis of disease severity could not be explained with routine hematological and genetic investigations. The clinical diagnosis of 'thalassemia intermedia' was justifiable as they had a β-thal mutation and disease severity that did not fit in with either β-thal trait or with β-thal major (β-TM). As mutations of α, β, and γ genes could not explain the unusual severity of the disease, further analysis with next-generation sequencing (NGS) for red cell diseases was carried out, which led to the diagnosis of coexisting membranopathies. This case series highlights the inherent difficulty in the diagnosis of β-TI with certainty in some patients where the genetic basis is not clear-cut.
Topics: Erythrocytes; Genotype; Humans; Mutation; alpha-Thalassemia; beta-Thalassemia
PubMed: 34612117
DOI: 10.1080/03630269.2021.1981370 -
Journal of Clinical Laboratory Analysis Dec 2021Thalassemia is a group of inherited autosomal recessive hemolytic anemia disease caused by reduced or absent synthesis of globin chain/chains of hemoglobin. Only few... (Comparative Study)
Comparative Study
BACKGROUND
Thalassemia is a group of inherited autosomal recessive hemolytic anemia disease caused by reduced or absent synthesis of globin chain/chains of hemoglobin. Only few studies showed the molecular characterization of α- and β-thalassemia in Meizhou city of China.
METHODS
A total of 22,401 individuals were collected; hematological and hemoglobin electrophoresis analysis and thalassemia genetic testing were performed.
RESULTS
Eleven thousand and thirty (49.24%) cases with microcytosis (mean corpuscular volume (MCV) < 82 fl), 11,074 (49.44%) cases with hypochromia (mean corpuscular Hb (MCH) < 27 pg) in 22,401 subjects, 11,085 cases with abnormal hemoglobin results were identified in subjects aged ≥6 months. 7,322 (32.69%) subjects harbored thalassemia mutations, including 4,841 (21.61%) subjects with α-thalassemia, 2,237 (9.99%) with β-thalassemia, and 244 (1.09%) with α-thalassemia combined β-thalassemia. 18 genotypes of α-thalassemia mutations and 27 genotypes of β-thalassemia mutations were characterized. The most frequent α gene mutation was -- (64.69%), followed by -α (19.93%), -α (7.73%), α α (3.97%), and α α (2.83%). The six most common β-thalassemia mutations were IVS-II-654 (C>T) (39.79%), CD41-42 (-TCTT) (33.02%), -28 (A>G) (10.38%), CD17 (A>T) (9.08%), CD27-28 (+C) (2.14%), and CD26 (G>A) (2.02%). In addition, MCV and MCH were sensitive markers for α- and β-thalassemia except for -α /αα, -α /αα, α α/αα, α α/αα, and β /β .
CONCLUSIONS
The -- , -α , and -α deletions were the main mutations of α-thalassemia, while IVS-II-654 (C>T), CD41-42 (-TCTT), -28 (A>G), and CD17 (A>T) mutations of β-thalassemia in Meizhou. There were some differences in thalassemia mutation frequencies in Meizhou city from other populations in China.
Topics: Asian People; China; Cities; Erythrocyte Indices; Gene Frequency; Genotype; Hemoglobins; Humans; Mutation; Mutation Rate; alpha-Thalassemia; beta-Thalassemia
PubMed: 34752669
DOI: 10.1002/jcla.24105